Environmental causes Flashcards
7 examples
Tabacco, weight/diet, Alcohol, UV, pesticides, oestrogens, solvents
how many substances are suspected/ known to cause cancer (2002)
228
what is the latent period
a fixed time between exposure and appearance of malignancy
what is the concept of age at expression
regardless of age at exposure, induced tumours will tend to be expressed at the same time as those which occur spontaneously
In 2015 how many deaths were due to tobacco in the UK
21% of all deaths
what % of cancer is caused by cigarette smoking
15%
2 carcinogens in cigarette smoke
Benzene and Acrolein
what increases the risk of mouth, voice box and oesophagus cancer in smokers
drinking more than 2 drinks/day (alcohol)
5 cancers strongly linked to being overweight/ physical inactivity
breast, endometrium, kidney, colon and oesophagus
what % of major cancers is accounted for by inactivity and obesity
25-30%
UV radiation and cancer
from sun, tanning beds etc… causes premature ageing of the skin and DNA damage that leads to melanoma
what does UV do to the DNA
it makes pyrimidine dimers form, causing a kink in the DNA, stalling replication, nucleotide excision repair used (but doesn’t always work)
what is the major carcinogenic wavelength
UVB 290-320
xeroderma pigmentosum (XP)
increased sensitivity to killing by UV radiation and UV-mimetic chemicals
what does classical XP exhibit
a defect in nucleotide excision repair
what is complete carcinogen
when it initiates and promotes activities
UVB effects on local and systemic immune function in skin
it dampens the immune system, decreasing immune response
how many ingredients in pesticides are found to be carcinogenic agents
at least 20
3 examples of banned pesticides
ethylene oxide, DDT and hexachlorobenzene
what cancers are caused by pesticides usually (7)
blood & lymphatic, lip, stomach, lung, brain, prostate and melanoma
HPV and cancer
causes cervical and anal cancer, women who have sex at 16 or many sexual partners are at increased risk
Hep B and C and cancer
major causes of liver cancer, risk factors are exposure to blood products, injection drug use and unprotected sex w many partners
EBV (epstein-barr) and cancer
linked to some lymphomas
Kaposi’s sarcoma-associated herpesvirus (KSHV) and cancer
linked to kaposi’s sarcoma and occurs through close person-to-person contact
oestrogens and cancer
HRT is linked to endometrial cancer, breast cancer and a reduction in colon cancer. taken in combo w progesterone can protect against risk
what is tamoxifen
a SERM used to prevent recurrence of ER+ breast cancer after treatment
what risks are associated with tamoxifen
increased risk of stroke, endometrial cancer and blood clots
what did Diethylstilbestrol (DES) do to women’s daughters
those that were exposed before birth to DES had more chance of developing a rare cervical and vaginal cancer.
what was DES
synthetic form of oestrogen prescribed to pregnant women
immunosuppressants and cancer (+ 2 examples)
cyclosporin and azathioprine are associated with increased cancer risks such as lymphoma
aspirin and cancer
regular consumption can lead to reduced risk of colon cancer
benzene and cancer
causes leukaemia in humans, inhaling contaminated air is the primary method of exposure e.g. in petrol stations
what are dioxins
unwanted byproducts of chemical processes that contain Cl and hydrocarbons, they accumulate in fats and break down slowly
what dioxin is known to be particularly carcinogenic
TCDD (2,3,7,8 - tetrachlorodibenzo-pdioxin)
how is the general population exposed to TCDD
eating dairy products, fish, meat inc. poultry
polycyclic aromatic hydrocarbons (PAHs) and cancer
exposure to them increases incidence of lung, skin and urinary cancer
what is the primary source of PAHs
burning wood and fuel for homes
examples of PAHs (2)
pyrene and benzo(a)-pyrene
asbestos and cancer
asbestos fibres lead to increased rates of mesothelioma (cancer of lung lining)
what was the cause of the largest % of occupational cancer
asbestos fibres
3 main hypotheses regarding the pathogenesis of asbestos induced mesothelioma
- the oxidative stress theory
- the chromosome tangling theory
- the theory of adsorption of many specific proteins as well as carcinogenic molecules
explain the oxidative stress theory as a hypothesis regarding the pathogenesis of asbestos induced mesothelioma
based on the fact that phagocytic cells that engulf asbestos fibres produce large amounts of free radicals because they cant digest the fibres.
- iron-containing asbestos fibres appear more carcinogenic
explain the chromosome tanging theory as a hypothesis regarding the pathogenesis of asbestos induced mesothelioma
asbestos fibres damage chromosomes when cells divide
explain the theory of adsorption of many specific proteins as well as carcinogenic moleules as a hypothesis regarding the pathogenesis of asbestos induced mesothelioma
asbestos fibres in vivo concentrate proteins or chemicals including the components of cigarette smoke
which metals are classified as group 1 carcinogens (4)
Arsenic, cadmium, chromium, nickel
what is a mechanism of heavy metal-induced damage
oxidative stress caused by reactive oxygen species (ROS)
what happens when exposed to ROS
- disruptions in tumour supressor gene expression
- damage repair processes
- enzymatic activities concerned in metabolism via oxidative damage
cancer associated with beryllium
lung
cancer associated with arsenic (5)
skin, lung, bladder, kidney, liver
cancer associated with cadmium
lung
cancer associated with chromium
lung
cancer associated with lead (2)
kidney, brain
cancer associated with nickel (2)
nasal cavity, lung
how do toxic metals interact with proteins?
bind to protein sites that they’re no meant to (e.g. transporters) which induces oxidative stress
what happens as a result of toxic metals interacting with proteins
oxidative deterioration of biological macromolecules e.g. DNA.
what are aflatoxins
cancer causing substances produced by certain types of fungi growing on food
what foods do aflatoxins commonly grow on
peanuts and grains
what cancer is associated with aflatoxins
liver
why is there a higher risk of aflatoxins in developing countries
there is no screening for the fungus
what is vinyl chloride
a colourless gas used by the plastics industry
what cancers are associated with vinyl chloride
lung, angiosarcomas of the liver and brain
what ionising radiation can both cause and ‘cure’ cancer
x-rays, gamma rays, alpha particles, beta particles, protons and neutrons
what is Ataxia telangiectasia (AT) A.K.A louis-barr syndrome
an autosomal recessive disorder referred to as a genome instability or DNA damage response syndrome
how is AT usually characterised (4)
cerebellar degeneration, telangiectasia immunodeficiency, radiation hypersensitivity and cancer susceptibility
what cancers are associated with AT
lymphomas and leukaemia, carriers can have GI and breast cancers
how is DNA damage induced by environmental mutagens resolved?
disparate repair and/or replicative pathways
what is the NCI GDC
cancer analysis system, is used to analyse data and compare data sets in the GDC
